Isotropic volumetric MRI for displaying cranial perineural spread of cranial nerve in nasopharyngeal carcinoma

Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal carcinoma were prospectively enrolled.MR scanning,including three-dimensional liver acquisition with volume acceleration-flexible(3D LAVA_Flex)image,T2WI with fat suppression(T2WI-FS),T1WI,contrast enhancement(CE)T1WI-FS of nasopharynx and neck region were performed.The displaying rates of CN PNS were evaluated and compared between 3D LAVA_Flex and T2WI-FS,T1WI,CE-T1WI-FS at patient level,CN group level and neural level,respectively.Results The displaying rate of CN PNS in all 87 nasopharyngeal carcinoma patients by 3D LAVA_Flex sequence was 49.43%(43/87),higher than that of conventional MRI(30/87,34.48%,P=0.001).Among 59 patients with advanced nasopharyngeal carcinoma diagnosed with conventional sequences,the displaying rate of CN PNS was 71.19%(42/59)by 3D LAVA-Flex sequence,higher than that of conventional MRI(30/59,50.85%,P=0.001).At both patient level and posterior CN level,significant differences of the displaying rate of CN PNS were found between 3D LAVA-Flex sequence and T2WI-FS,T1WI,CE-T1WI-FS,while at CN level,the displaying rates of mandibular nerve PNS,CNⅨ—ⅪPNS in jugular foramen(P<0.05)and CNⅨ—ⅫPNS in carotid space of 3D LAVA_Flex sequence were all significantly higher than that of T2WI-FS,T1WI and CE-T1WI-FS(all P<0.05),of PNS of CNⅢ—Ⅴin cavernous sinus were higher than that of T2WI-FS(P<0.05),while of PNS of hypoglossal nerve were significantly higher than that of T2WI-FS and T1WI(both P<0.05).Conclusion 3D LAVA_Flex sequence could be used to effectively display CN PNS of nasopharyngeal carcinoma.

Signal intensity changes of dentate nucleus on plain MR T1WI innasopharyngeal carcinoma patients after radiotherapy andmultiple injections of gadolinium-base contrast agent

Objective To observe changes of plain MR T1WI signal intensity of dentate nucleus in nasopharyngeal carcinoma patients after radiotherapy and multiple times of intravenous injection of gadolinium-based contrast agent(GBCA).Methods Fifty patients with pathologically confirmed nasopharyngeal carcinoma and received intensity-modulated radiotherapy were retrospectively enrolled as the nasopharyngeal carcinoma group,and 50 patients with other malignant tumors and without history of brain radiotherapy were retrospectively enrolled as the control group.All patients received yearly GBCA enhanced MR examinations for the nasopharynx or the head.T1WI signal intensities of the dentate nucleus and the pons on same plane were measured based on images in the year of confirmed diagnosis(recorded as the first year)and in the second to the fifth years.T1WI signal intensity ratio of year i(ranging from 1 to 5)was calculated with values of dentate nucleus divided by values of the pons(ΔSI i),while the percentage of relative changes of year j(ranging from 2 to 5)was calculated withΔSI j compared toΔSI 1(Rchange j).The values of these two parameters were compared,and the correlation ofΔSI and GBCA injection year-time was evaluated within each group.Results No significant difference of gender,age norΔSI 1 was found between groups(all P>0.05).The second to the fifth yearΔSI and Rchange in nasopharyngeal carcinoma group were all higher than those in control group(all P<0.05).Within both groups,ΔSI was positively correlated with GBCA injection year-time(both P<0.05).Conclusion Patients with nasopharyngeal carcinoma who underwent radiotherapy and multiple times of intravenous injection of GBCA tended to be found with gradually worsening GBCA deposition in dentate nucleus,for which radiotherapy might be a risk factor.

Expression of Cyclooxygenase-2 in Nasopharyngeal Carcinoma and Its Relation to Angiogenesis and Prognosis

Objective： The purpose of this study was to evaluate cyclooxygenase-2 （COX-2） expression in nasopharyngeal carcinoma （NPC） and its correlation with clinicopathologic features, angiogenesis, and prognosis. Methods： The expressions of COX-2 and vascular endothelial growth factor （VEGF） and microvascular density （MVD） were determined with immunohistochemical methods in eighty-six NPC patients followed up over 5 years. Results： Sixty-three tumors （73.3%） were classified as COX-2 positive. COX-2 expression was positively related to VEGF expression （r=0.438, P〈0.01） and correlated with the tumor pathological grade, extent of primary lesion, lymph node metastasis, distant metastasis and shorter survival. Conclusion： Our results suggest that COX-2, being highly expressed and strongly correlated with angiogenesis in nasopharyngeal carcinoma, is apt to be used as a predictor of prognosis, including local recurrence and distant metastasis.

Effect of heparin on apoptosis in human nasopharyngeal carcinoma CNE2 cells

In order to study the mechanism of the effect of heparin on apoptosis in carcinoma cells, the nasopharyngeal carcinoma cell line CNE2 was used to identify the effect of heparin on apoptosis associated with the expression of c-myc, bax, bcl-2 proteins by use of Hoechst 33258 staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), agarose gel electrophoresis, and flow cytometry, as well as Western blot analysis. The results showed that heparin induced apoptosis of CNE2 cells including the morphologic changes such as reduction in the volume, and the nuclear chromatin condensation, as well as the 'ladder pattern' revealed by agarose gel electrophoresis of DNA in a concentration-dependent manner. The number of TUNEL-positive cells was dramatically increased to 33.6+/-1.2% from 2.8+/-0.3% by treatment with heparin in different concentrations (10 to approximately 40 kU/L). The apoptotic index was increased to 32.5% from 3.5% by detecting SubG1 peaks on flow cytometry. Western blot analysis showed that levels of bcl-2, bax and c-myc were significantly overexpressed by treatment with the increase of heparin concentrations. These results suggest that heparin induces apoptosis of CNE2 cells, which may be regulated by differential expression of apoptosis-related genes.

CHEMOTHERAPY FOR ADVANCED NASOPHARYNGEAL CARCINOMA WITH METHOTREXATE, VINCRISTINE, CISPLATIN AND ADRIAMYCIN

Objective: To evaluate the efficacy and toxicity of M-VCA (methortrexate 30 mg/m2, vincristine 2 mg, cisplatin 70 mg/m2, adriamycin 30 mg/m2) combination chemotherapy for advanced nasopharyngeal carcinoma. Methods: Thirty-five patients with advanced nasopharyngeal carcinoma, including 11 patients with untreated local advanced nasopharyngeal carcinoma and 24 patients with local-regional recurrent or metastatic nasopharyngeal carcinoma, received the chemotherapy of M-VCA. The cycle was repeated on day 22 for two cycles. All patients completed the chemotherapy courses. Results: The overall response rate was 75%, with untreated local advanced nasopharyngeal carcinomas 11/11(100%), local-regional recurrent nasopharyngeal carcinomas 12/18(67%), lung metastases 8/9(89%), bone metastases 5/9(56%), and liver metastases 1/2(50%). The main side effects included mild to moderate degree alopecia, nausea/vomiting, and neutropenia. Conclusion: M-VCA is well tolerated and has good efficacy for advanced nasopharyngeal carcinoma and is worth investigating further.

THREE-DIMENSIONAL CONFORMAL RADIATION THERAPY FOR LOCALLY RECURRENT NASOPHARYNGEAL CARCINOMA

Objective: To investigate the safety and effectiveness of three-dimensional conformal radiation therapy (3-D CRT) for locally recurrent nasopharyngeal carcinoma (NPC). Methods: From April 1998 to March 2000, 34 patients who had undergone previous external beam radiation therapy were retreated with 3-D CRT for locally recurrent NPC (33 poorly differentiated squamous cell carcinomas, 1 adenoma). The patients were re-staged according to Huaqing staging system with the following distribution: T1N0M0 in 5 cases, T2N0M0 in 11 cases, T3N0M0 in 12 cases, T4N0M0 in 6 cases. The maximal dimension of the gross tumor volume (GTV) ranged from 1.0 cm to 5.0 cm (median: 2.9 cm). CT simulation and 3-D planning were used to ensure full and conformal coverage of the planning target volume (PTV) by treated volume, while minimizing the absorbed dose of the adjacent normal tissue. 5–7 static conformal coplanar or noncoplanar portals were delivered for each fraction irradiation. The total dose delivered ranged from 65–70 Gy, with 2.5 Gy per fractionation, one fractionation per day, 5 days a week. Median follow-up time from 3-D CRT was 25 months (range: 12–36 months). Results: Over the follow-up period, local recurrence was observed in 3 patients, regional failure in 3, distant metastasis in 3, and six patients died; 88.2% (30/34) of the patient maintained local control, 82.4% (28/34) survived, and 76.5% (26/34) survived with no evidence of tumor. Acute complications were minor and few. The overall incidence of late complication was 20.6% (7/34), and severe complication was 14.7% (5/34), after re-irradiation with 3-D CRT. Conclusion: 3-D CRT is safety and effectiveness for most of the patients with locally recurrent NPC. Our preliminary results indicate a high local control rate and a low complication rate. The long-term curative effect and sequelae await further study.

A Survey of Researches on Synergy and Toxicity Abatement of Traditional Chinese Medicine in Radiotherapy of Nasopharyngeal Carcinoma

Even though radiotherapy is a therapy of first choice in the treatment of nasopharyngeal carcinoma, its radiotoxicity is often difficult to bear for patients in addition to the unsatisfactory effect in some patients. Therefore, an important problem in the treatment of nasopharyngeal carcinoma is to abate radiotherapeutic toxicity and improve its effect. Some progresses in promoting the effect of radiotherapy and abating its toxicity have been made through application of traditional Chinese medicine (TCM) which is briefly reviewed as follows.

A PROPOPSAL CONCERNING THE HISTOLOGICAL TYPING OF PRIMARY NASOPHARYNGEAL CARCINOMA

A proposal concerning the histological typing of primary nasopharyngeal carcinoma is offered in order to coincide with pathologic terms used both by Chinese and foreign pathologists and reflect the achievements in the research field of NPC. This proposal was worked out mainly basing upon the authors’ diagnostic experience gained in the past 30 years and the international criteria for tumor classification. Primary nasopharyngeal carcinoma could be classified into four major types, namely, keratinizing squamous cell carcinoma (KSCC), non- keratinizing carcinoma (NKC), adenocarcinoma (AC) and carcinomain-situ (CIS). KSCC could be graded as being well, moderately and poorly differentiated according to the amount of keratinization and intercellular bridges presented in the biopsy slide. The NKC is the most frequent type seen in the high-incidence area of NPC, and could also be subdivided into differentiated and undifferentiated variants. Actually, three grades of KSCC and two variants of NKC are a reflection of different degrees of squamous differentiation. They are consistently associated with Epstein-Barr virus (EBV) infection. There are two major categories of nasopharyngeal AC, namely, traditional and salivary-gland type. As contrasted with KSCC and NKC, nasopharyngeal AC is rarely infected with EBV. There are two subtypes of CIS, namely, squamous- and columnar-cell type. The histological typing concerning the primary nasopharyngeal carcinoma offered above is really a practical proposal and also coincided with the international usage. This proposal can be mastered easily and the authors recommend its routine use in diagnostic pathology.

THE INTRACELLULAR FORM OF EPSTEIN-BARR VIRUS GENOME IN NASOPHARYNGEAL CARCINOMA

This work was supported by the National Natural Science Foundation of China (No. 39370766). Object: To study the existent form of EBV genome in nasopharyngeal carcinoma (NPC) biopsies, in a trans planted NPC tumor SUNT 1 and its corresponding epithelial cell line SUNE 1. Methods: By using polymerase chain reaction (PCR) amplification of Epstein Barr virus (EBV) BamHI W fragment, EBV DNA was detected in 20/20 biopsy specimens of poorly differentiated, as well as in a nude mouse xenografted NPC tumor (SUNT 1, from passage 1 to 34) and in the corresponding epithelial cell line (SUNE 1, from passage 1 to 62). The intracellular form of EBV genome was studied by analyzing the terminal structure using a LMP2A probe and an “ in situ lysing gel” technique. Results: A single EBV fused terminal DNA fragment was detected in 19 biopsy specimens, two hybridized bands were seen in one specimen. These results indicate that an episomal form of EBV genome is predominantly present in most NPC biopsy specimens, but insertion of the genome into the host chromosome could not be excluded. Conclusion: The finding suggests that EBV infection precedes clonal amplification of transformed cells, or in a rare case, that a single EBV infected clone is predominant in the development of NPC. Linear form of EBV DNA was detected in the 20th passage of SUNE 1; this may imply the in vitro activation of the productive cycle of EBV.

Comparison of efficacy between two boost treatments in residual tumor of nasopharyngeal carcinoma after radical radiotherapy

Objective： To compare the efficacy between stereotactic radiotherapy （SRT） and intracavitary brachytherapy （brachytherapy） in residual tumor of nasopharyngeal carcinoma （NPC） after treating with conventional external beam radiotherapy. Methods： 60 patients with residual tumor of NPC after radical external beam radiotherapy （range 68 to 72 Gy） were randomized into SRT group （27 patients） and brachytherapy group （33 patients）. Patients in SRT group received boost treatment of 10-20 Gy, 2-3 fractions, once every other day; patients in brachytherapy group were treated with boost 10-20 Gy, 5 Gy per fraction, twice a week. Results： Efficacy in the near future： in SRT group, the complete recession （CR）, partial recession （PR） and no change （NC） rates were 77.8% （21/27）, 18.5% （5/27）, 3.7% （1/27）, respectively and the efficacy rate was 96.3% （CR ＋ PR）; in brachytherapy group： the CR, PR and NC rates were 75.8% （25/33）, 18.2% （6/33）, 6.1% （2/33）, respectively and the efficacy rate was 93.9% （CR ＋ PR）. The efficacy rates of the above two groups were compared （x^2 = 0.032, P 〉 0.05）. Long term efficacy： in SRT group, 1-year and 3-year survival rates were 96.3%, 66.5% respectively and the median live time was 48 months; in brachytherapy group： 1-year and 3-year survival rates were 93.9%, 60.2% respectively and the median live time was 46 months. The survival rates of two groups were compared （x^2 = 0.172, P 〉 0.05）. Conclusion： Both boost techniques of SRT and brachytherapy had elevated efficacy in patients with residual tumor of NPC and there was no obvious difference between the efficacy of the near and long term in SRT and brachytherapy group.

Technical and Dosimetric Study of Four Facio-cervical Fields Conformal Radiotherapy for Nasopharyngeal Carcinoma

Objective： The aim of this study is to establish the methods of four facio-cervical fields＇ conformal radiotherapy （4F-CRT） for nasopharyngeal carcinoma （NPC）, and to optimize the methods for clinical practice. Methods and Materials： 40 patients with untreated NPC of T1-T4 （1997AJCC Staging System） were rolled into this study. Conventional and four ratio-cervical fields conform plans were designed for each patient using Pinnacle 8.0 three-dimension treatment planning system （3D-TPS）： 1） Improved plan, four ratio-cervical fields＇conform plans, anterior, posterior ratio-cervical and 2 lateral opposing facio-eervical fields; 2） Conventional plan, two lateral opposing facio-cervical fields only with the same dose delivered to the target in each plan, close volume histograms （DVHs） of the targets and normal organs, brain stem, spinal cord, parotid glands, and temporal mandibular joints （TMJs） were compared and the dose distribution were evaluated. Results： 1） The dose distribution of the improved plan could meet the requirements for the target volume. 2） There was not any significant difference in the dose of spinal cord between the two plans. The mean doses of Dmax for brain stem in conventional plan were much lower than those in the improved plan, though both were within safety limits. 3） Compared with the conventional plans, the improved plan significantly decreased the hotspot areas in the target volume and had better parotid glands and temporal mandibular joints sparing effect. Conclusion： Compared with the conventional plan, the improved plan provides satisfactory dose coverage to the tumor volume and better sparing of the parotid gland, TMJs and other normal tissues in external beam radiotherapy of NPC.

鼻咽部髓外浆细胞瘤1例

1临床资料患者,女,54岁,主因渐进性鼻塞1年余入院。患者夜间睡眠时张口呼吸伴打鼾,偶有头痛,无发热、血涕、耳鸣及听力下降。鼻内镜检查:右侧鼻咽部淡红色新生物,表面不光滑,质韧,堵塞全部右侧后鼻孔及大部分、左侧后鼻孔,基底位于右侧咽隐窝处(图1A)。耳内镜检查发现右耳鼓膜内陷,入院诊断为鼻咽部肿物。

新辅助化疗联合同期放化疗治疗局部晚期鼻咽癌的毒副反应及近期疗效(英文)

Background and Objective:Concurrent chemoradiation therapy(CCRT) is the standard treatment for patients with locally advanced nasopharyngeal carcinoma(NPC).The effect of neoadjuvant chemotherapy followed by CCRT has not been determined.Therefore,we conducted 2 phase Ⅱ studies to evaluate the efficacy and safety of neoadjuvant chemotherapy with a regimen of docetaxel,cisplatin,and 5-fluorouracil(5-Fu)(TPF) followed by radiotherapy and concurrent cisplatin in patients with stage-Ⅲ and -Ⅳ(A -B) NPC.This article is the preliminary report on treatment-related toxicities and response.Methods:Graded according to the 2002 American Joint Committee on Cancer(AJCC) staging criteria,only patients with stage-Ⅲ or -Ⅳ(A-B) poorly differentiated or undifferentiated NPC(World Health Organization type Ⅱ/Ⅲ) were included.We planned to recruit 52 patients with stage-Ⅲ disease and 64 patients with stage-Ⅳ(A-B) disease.All patients received neoadjuvant chemotherapy with TPF(docetaxel 75 mg/m2,day 1;cisplatin 75 mg/m2,day 1;5-Fu 500 mg/(m2·day),continuous intravenous infusion for 120 h),every 3 weeks for 3 cycles,followed by weekly cisplatin(40 mg/m2) concurrent with radiotherapy.Three-dimensional conformal radiotherapy(3D-CRT) and intensity-modulated radiotherapy(IMRT) were used.Gross disease planning target volume(PTV),high-risk and low-risk subclinical PTV doses were prescribed at 70-76 Gy,66-70 Gy,and 60-61.25 Gy at 1.75-2.0 Gy per fraction.The lower neck or supraclavicular fields may be treated with conventional AP/PA fields for a total of 54 Gy at 1.8 Gy per fraction.Patients were evaluated for tumor response after the completion of neoadjuvant chemotherapy,and at 3 months after radiation according to the Response Evaluation Criteria In Solid Tumors(RECIST).The latest version of the National Cancer Institute's Common Terminology Criteria for Adverse Events(NCI CTCAE 3.0) was used for grading all adverse events.Results:Fifty-nine patients were evaluable for treatment response.Thirty patients had stage-III disease and 29 patients had stage-IV(A-B).All patients completed RT to the prescribed dose and 2 cycles of neoadjuvant chemotherapy,with 51 patients(86.4%) completing 3 cycles.A total of 50(84.7%) and 39 patients(66.1%) completed 4 weeks and 5 weeks of cisplatin during CCRT,respectively.The overall response rate in the primary site and the neck region were 94.9% [complete response(CR) in 25.4%] and 100%(CR in 19.6%) after completing neoadjuvant chemotherapy.At 3 months after RT,the CR rates increased to 96.6% and 90.2%,respectively.After a median follow-up of 14.3 months,we observed 5 treatment failures and 2 deaths.The 1-year overall survival,distant metastasis-free survival,and locoregional relapse-free survival rates were 100%,95.7%,and 97.7%,respectively.The rates of grade 3/4 myelosuppression and anorexia/nausea/vomiting during neoadjuvant chemotherapy were 55.9% and 16.9%,respectively.The corresponding rates were 11.9% and 23.7% during CCRT.Grade 3/4 mucositis,skin desquamation,and xerostomia occurred in 6.8%,44.1%,and 27.1% of patients,respectively.There were no treatment-related deaths.Conclusions:Neoadjuvant chemotherapy with TPF followed by CCRT was well tolerated with a manageable toxicity profile.Preliminary results are encouraging and warrant further investigation.

RADIATION-INDUCED APOPTOSIS OF TWO NASOPHARANGEALCARCINOMA CELL LINES

Objective: To study apoptosis induced by radiation in two nasopharyngeal carcinoma (NPC) cell lines, CNE and CNE-2. Methods: Hoechst 33342 staining, immuno-histochemical staining, RT-PCR, DNA dot blotting and Southern blotting were used to identify apoptosis. Results: A single dose of X-irradiation resulted in apoptosis, the apoptotic index (AI) was time- and dose-dependent. Different apoptotic responses existed in the two cell lines. Immunohistochemical staining showed that bcl-2 protein was strongly positive in CNE but negative in CNE-2. However, RT-PCR revealed p53 mRNA in CNE-2 but not in CNE. P53 and bcl-2 genes were both present in the two cell lines as shown by DNA blotting, but the 2.8 kb fragment of the p53 gene was much lower than the 5.6 kb fragment on CNE which was clearly shown in Southern hybridization, suggestive of partial deletion of p53 gene in CNE. Conclusion: Apoptotic response to radiation is different in two NPC cell lines. CNE is more radioresistant than CNE-2. Overexpression of bcl-2 protein and partial deletion of p53 gene may explain their difference in radiosensitivity.

A comprehensive review and characterization of nasopharyngeal carcinoma clinical trials

Objective:Although standard of care for primary nasopharyngeal carcinoma(NPC)is chemoradiotherapy,there remains no consensus on management of recurrent or metastatic disease.We characterized recent clinical trials on NPC to assess trends in NPC treatment and establish promising areas for future research.Study Design:Retrospective database study.Setting:ClinicalTrials.gov database.Methods:Retrospective review of all NPC trials from November 1999 to June 2021.For each study,the following variables were extracted:study characteristics,intervention,outcome measures,and inclusion criteria.Secondary searches via PubMed and Google scholar determined trial publication status.Results:A total of 448 clinical trials were identified:72(16%)observational and 376(84%)interventional,of which there were 30(8%)Phase I,183(49%)Phase II,86 Phase III(23%),and 5(1%)Phase IV trials.Fifty-four percent of trials included only primary NPC while 111(25%)exclusively studied recurrent cancers.The most common interventions were cisplatin(n=64)and intensity modulated radiation therapy(n=54);there were 38 trials involving PD-1 monoclonal antibodies.Thirty-four studies examined quality of life measures,including xerostomia and mucositis.Of the completed studies,53.2%have published manuscripts.Poor patient accrual was the most common reason for premature study termination.Conclusions:Novel immunotherapies have been increasingly incorporated into NPC studies in recent years,however,chemotherapy and radiation,despite their numerous side effects,are still widely used due to their clinical effectiveness.Future trials are warranted to determine the optimal therapeutic regimens to decrease relapse rates and side effects.

A clinical trial of active immunotherapy with anti-idiotypic vaccine in nasopharyngeal carcinoma patients

OBJECTIVE: To investigate the effect of active immunotherapy with anti-idiotypic vaccine in patients with nasopharyngeal carcinoma (NPC). METHODS: Anti-idiotypic antibodies (2H4/5D3) bearing the internal image of the NPC antigen were used in active immunotherapy in NPC patients receiving radiotherapy. Antibodies and cytokine levels in patient sera were determined using ELISA before and after active immunotherapy. IL-2 mRNA expression in the peripheral blood mononuclear cells (PBMC) was measured by in situ hybridization. RESULTS: Nineteen patients with NPC at stage IV were treated with alum-precipitated 2H4 or 5D3. Neither hypersensitivity nor adverse side effects were observed. The levels of anti-anti-idiotypic antibodies (Ab3) and anti-NPC antibodies (Ab1') were increased. Human anti-mouse antibodies (HAMA) were seen in 19 patients of the experimental group; the levels of Ab1' did not increase in the control group. Serum IL-2, IFN-gamma and TNF-alpha levels were increased in most patients in the experimental group, while no differences were observed in Ab1' and cytokine levels between pre- and post-therapy in the control group. In addition, IL-2 mRNA expression in PBMCs from NPC patients was closely related to serum IL-2 (r = + 0.8829) levels by in situ hybridization. CONCLUSIONS: Anti-idiotype vaccine is safe for clinical active immunotherapy. Anti-idiotypic vaccine might be able to enhance humoral and/or cellular immunity in NPC patients receiving radiotherapy.

High frequency loss of heterozygosity on the long arms of chromosomes 13 and 14 in nasopharyngeal carcinoma in Southern China

OBJECTIVE: To investigate the loss of heterozygosity (LOH) on chromosomal arms 13q and 14q in nasopharyngeal carcinoma (NPC) using 21 microsatellite polymorphic markers and to study whether there is a correlation between LOH and clinicopathologic parameters and/or Epstein-Barr virus (EBV) infection in NPC. METHODS: Sixty cases of NPC were studied using polymerase chain reaction based microsatellite analysis with genescan and genotyping techniques. RESULTS: LOH was detected on 13q in 78% of NPC tumors, high frequency LOH loci (more than 30%) clustered to 13q12.3-q14.3 and 13q32. On chromosome 14q, LOH was detected in 80% of NPC tumors; high frequency LOH loci clustered to 14q11-q13, 14q21-q24 and 14q32. High frequency LOH at 13q31-q32 correlated with a lower level of EBV infection; LOH on chromosome 14q was closely associated with poor differentiation of NPC tumor cells. CONCLUSION: Our results suggest that in NPC, LOH on chromosome 13q and 14q are common genetic events, and putative tumor suppressor genes (TSG) residing in these regions may be involved in tumorigenesis.

Detection of Epstein-Barr virus DNA in plasma/serum:a useful serological indicator for diagnosis of nasopharyngeal carcinoma

OBJECTIVE: To compare the detection rates of Epstein-Barr virus (EBV) DNA in the serum/plasma between apparently healthy adults (AHAs) and nasopharyngeal carcinoma (NPC) patients in attempt to evaluate the efficiency of EBV DNA assay for serodiagnosis of NPC. METHODS: The plasma and serum were obtained from 58 AHAs and 66 untreated NPC patients. EBV DNA W-fragment was detected using nested ploymerase chain reaction (PCR). Immunoenzymatic assay for titration of IgA-VCA was also adopted. RESULTS: EBV DNA detection rate (84.85%) in the plasma/serum of 66 NPC patients was significantly higher than that (10.34%) in 58 AHAs. The sensitivity of plasma/serum EBV DNA assay (0.8485) was higher than that (0.8030) of titrating IgA-VCA (positive criterion >/= 1:40) though the specificities of these two tests were the same (0.8966). The correct rate, predictive value of a positive test, and Odds ratio of dual positivity (0.8387, 0.9792 and 141.0, respectively) were higher than those of single positivity either to plasma/serum EBV assay (0.5242, 0.7333 and 1.1423, respectively) or to IgA-VCA >/= 1:40 test (0.4839, 0.5385 and 1.0480, respectively). CONCLUSION: The EBV DNA detection in the plasma/serum using nested PCR may be a useful indicator for serodiagnosis of NPC.

Molecular cloning and characterization of NAG-7: a novel gene downregulated in human nasopharyngeal carcinoma

Objective To identify novel tumor suppressor genes at chromosome 3p24-26 in human nasopharyngeal carcinoma (NPC).Methods Twenty epithelial-derived expressed sequence tags (EST) were selected from chromosome 3p24-26. RT-PCR and Northern blot were used to detect the expression of the ESTs in NPC cell line, HNE-1, and primary cultures of normal nasopharyngeal epithelial cells. One EST, which was substantially downregulated in the HNE-1 cell line, was detected in 19 NPC biopsy samples, cDNA library screening was used to get its full sequence and the sequence of this novel gene was analyzed.Results A novel gene located at chromosome 3p25.3 was obtained and named NAG-7. It was downregulated in 26.3％ (5/19) of NPC biopsy samples. Its 1677 bp full length cDNA had a potential open reading frame predicting a 94 amino acid protein with a molecular weight of 11023.87 Dalton. Analysis of the NAG-7 gene showed that it was a transmembrane protein containing a protein kinase C phosphorylation site and a myristyl site. It has no significant homology to any reported genes in the database of GenBank. Conclusion NAG-7 is a novel gene downregulated in NPC, suggesting that it may be involved in the development of NPC.

Post-radiation CT changes and recurrent nasopharyngeal carcinoma

Background Nasopharyngeal carcinoma （NPC） is endemic in Southern Asia. Radiation therapy remains the mainstay of treatment strategies for NPC. Although approximately 19%-56% of patients develop a recurrent disease 5 years after their primary treatment, recognition of post-radiation changes and early detection of relapse are important in improving the outcome of NPC. Our aim was to analyze the post-radiation changes and recurrent diseases related to NPC using computed tomography （CT） scans and to investigate their relationship. Methods CT scans of 510 pathologically proven NPC patients who have been followed up for more than 2 years after radiation were reviewed. The tumor＇s response to the radiation therapy and its relevance to recurrence were evaluated. Results For patients who were followed up for more than 2 years, their CT scans-obtained within 3 months, during the 4th to the 6th month, and beyond 7 months after radiation therapy, showed a normal nasopharyngeal cavity with a slight thickening in the wall in 93.5%, 95.0% and 84.8% of the patients respectively. The degree of tumor regression had no significant relevance to the risk of recurrence within the initial 3 months （P=0.094）. During this term, the relapse rates in the cases in which the nasopharyngeal walls were displayed as normal, slightly or moderately thickening, or with obvious residual masses on CT scans were 7.1%, 11.7%, 23.5% and 23.1% respectively. The degree of tumor regression beyond 3 months after radiation therapy had a considerable reverse relevance to the risk of recurrence （P=-0.000）. The relapse rates were 13.2%, 14.1%, 10.2% and 2.1%, respectively, in the cases with a normal and a slightly thickening nasopharyngeal wall during the 4th to the 6th month, the 7th to the 12th month, the 13th to the 24th month, and beyond 25 months after radiation. In contrast, the percents in cases with moderate or more aggressive thickening walls in the corresponding periods were 62.5%, 88.9%, 100% and 100%. Within 6 months after radiation therapy, shown by CT scans the metastatic lymph nodes disappeared, markedly decreased, slightly decreased, or enlarged in 37.4%, 51.8%, 4.7%, and 0.4%, respectively, of the patients. During 6 to 12 months after radiation therapy, the proportions were 78.5%, 19.2%, 0.6% and 1.7% correspondingly. Beyond 12 months, the proportions were 83.7%, 7.9%, 0%, and 8.4%. The regression degree of the malignant nodes after radiation therapy showed a remarkable reverse relevance to the risk of recurrence in lymph nodes （P=0.000）. In the cases with disappearing, markedly decreased, slightly decreased, or enlarged malignant nodes within six months after radiation, the relapse rates were 2.9%, 4.5%, 12.5% and 100%, respectively. Conclusions If the nasopharyngeal walls are shown to remain moderately thick on a CT scan beyond 6 months after radiotherapy, the risk of relapse will increase. The baseline images taken within 3 months after radiotherapy and regular follow-uo studies are the kev to pick up the tumor recurrences in an earlier stage.